title: [Mitochondrial tRNAThr G15927A mutation may influence the phenotypic manifestation of deafness-associated 12S rRNA A1555G mutation.].
abstract: We report here the clinical and genetic evaluations as well as mutational analysis of mitochondrial DNA (mtDNA) in a four-generation Chinese Han family with aminoglycoside-induced and nonsyndromic hearing loss. Strikingly, this family exhibited a high penetrance and expressivity of hearing loss. The penetrances of hearing loss in this family were 75% and 41.7% respectively, when aminoglycoside-induced deafness was included or was excluded. The severity of hearing loss in matrilineal relatives varied from profound hearing loss to normal hearing. Mutational analysis of mtDNA identified the homoplasmic A1555G mutation and a distinct set of mtDNA variants belonging to the Asian haplogroup B5b. Of these, the G15927A mutation absent in 156 Chinese controls is localized at the anticodon-stem of tRNAThr at conventional position 42. The guanine at this position (G42) of tRNAThr is highly conserved from bacteria to human mitochondria. Thus, it is antici-pated that the G15927A disrupted the highly conserved C-G base-pairing at the anticodon-stem of tRNAThr. The alteration of structure of this tRNA likely leads to a failure in tRNA metabolism, thereby worsens the mitochondrial dysfunction asso-ciated with the A1555G mutation. Thus, the G15927A mutation has a potential modifying role in increasing the penetrance and expressivity of hearing loss associated with the deafness-associated 12S rRNA A1555G mutation in this Chinese pedigree.
authors.affiliation: Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou 325035, China E-mail: helen.mito@gmail.com.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Tang
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Li
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Lu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Rong-Hua
authors.initials: RH
authors.lastname: Li
authors.forename: Jin-Dan
authors.initials: JD
authors.lastname: Wang
authors.forename: Min-Xin
authors.initials: MX
authors.lastname: Guan
mesh_terms: D003638:Deafness / Q000235:genetics; D034381:Hearing Loss / Q000235:genetics; D006801:Humans; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012363:RNA, Transfer, Thr
chemical_list: D012363:RNA, Transfer, Thr